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- Title
Ethionamide Preconditioning Enhances the Proliferation and Migration of Human Wharton's Jelly-Derived Mesenchymal Stem Cells.
- Authors
Lee, Na-Hee; Myeong, Su Hyeon; Son, Hyo Jin; Hwang, Jung Won; Lee, Na Kyung; Chang, Jong Wook; Na, Duk L.
- Abstract
Mesenchymal stem cells (MSCs) are a useful source for cell-based therapy of a variety of immune-mediated diseases, including neurodegenerative disorders. However, poor migration ability and survival rate of MSCs after brain transplantation hinder the therapeutic effects in the disease microenvironment. Therefore, we attempted to use a preconditioning strategy with pharmacological agents to improve the cell proliferation and migration of MSCs. In this study, we identified ethionamide via the screening of a drug library, which enhanced the proliferation of MSCs. Preconditioning with ethionamide promoted the proliferation of Wharton's jelly-derived MSCs (WJ-MSCs) by activating phosphatidylinositol 3-kinase (PI3K)/Akt and mitogen-activated protein kinase/extracellular signal-regulated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK)1/2 signaling. Preconditioning with ethionamide also enhanced the migration ability of MSCs by upregulating expression of genes associated with migration, such as C-X-C motif chemokine receptor 4 (CXCR4) and C-X-C motif chemokine ligand 12 (CXCL12). Furthermore, preconditioning with ethionamide stimulated the secretion of paracrine factors, including neurotrophic and growth factors in MSCs. Compared to naïve MSCs, ethionamide-preconditioned MSCs (ETH-MSCs) were found to survive longer in the brain after transplantation. These results suggested that enhancing the biological process of MSCs induced by ethionamide preconditioning presents itself as a promising strategy for enhancing the effectiveness of MSCs-based therapies.
- Subjects
MESENCHYMAL stem cells; MITOGEN-activated protein kinases; PROTEIN kinases; CELL migration; PHOSPHATIDYLINOSITOL 3-kinases
- Publication
International Journal of Molecular Sciences, 2020, Vol 21, Issue 19, p7013
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms21197013